Melissa Whitworth

Social support, anxiety and depression after chemotherapy for ovarian cancer: a prospective study.

OBJECTIVES We aimed to describe the levels of anxiety and depression in patients during the 3 month period following the end of chemotherapy treatment and to identify factors that predict psychological morbidity. METHOD We performed a prospective study in women with ovarian cancer to determine the changes in psychological status in the 3 months following completion of chemotherapy. Sixty-three consecutive patients were assessed at the completion of chemotherapy (Time 1) and 57 at 3 months follow-up (Time 2). Relevant disease and patient characteristics were recorded and patients were assessed at Time 1 for anxiety, depression and their perception of emotional support, an index of their psychosocial environment. Anxiety and depression were re-assessed at Time 2. RESULTS The results indicate significant initial psychological morbidity, with clinical caseness for anxiety (38%) and depression (33%) being common. Follow-up at Time 2 shows that patients undergo a significant reduction in cases (19%) and symptoms of depression but an increase in cases of anxiety (47%). The principal factors associated with symptoms of anxiety at Time 2 were poor perceived social support, increased intrusive thoughts and, to a lesser extent, younger age. Medical parameters, such as the stage of disease, response of the cancer to treatment, Ca125 (a tumour glycoprotein) and Karnofsky Performance status (a measure of how well the patients is) were not associated with worse psychological outcome. CONCLUSION These data show for the first time that social support and intrusive thoughts, rather than physical parameters, are the principal determinants of psychological morbidity in patients with ovarian cancer.

Parents’ experiences and expectations of care in pregnancy after stillbirth or neonatal death: a metasynthesis

Pregnancy after perinatal death is characterised by elevated stress and anxiety, increasing the risk of adverse short‐term and long‐term outcomes.

Regulation of fibroblast growth factor-2 activity by human ovarian cancer tumor endothelium

Fibroblast growth factor-2 (FGF-2) is a potent angiogenic cytokine that is dependent on heparan sulfate for its biological activity. We have investigated the relationship among heparan sulfate, FGF-2, and the signal-transducing receptors in human, advanced-stage, serous ovarian adenocarcinoma. Using a unique molecular probe, FR1c-Ap, which consisted of a soluble FGF receptor 1 isoform lllc covalently linked to an alkaline phosphatase moiety, the distribution of heparan sulfate that had the ability to support the formation of a heparan sulfate/FGF-2/FGFR1 isoform IIIc alkaline phosphatase heparan sulfate construct complex was determined. This may be taken as a surrogate marker for the distribution of biologically active heparan sulfate and was distributed predominantly in endothelial cells and stroma but was absent from adenocarcinoma cells. In situ hybridization revealed the expression of FGFR1 mRNA in the endothelium and reverse transcription-PCR confirmed the presence of FGFR1 isoform IIIc but not isoform IIIb. The presence of FGF-2 around tumor endothelium was detected through immunohistochemistry. Double-staining techniques showed that heparan sulfate was found predominantly at the basal aspect of the endothelium and suggested that syndecan-3 might function as one of the proteoglycans involved in FGF-2 signaling in the endothelium. The data suggest that the entire extracellular signaling apparatus, consisting of FGF-2, biologically active heparan sulfate, and FGFRs capable of responding to FGF-2, is present in ovarian cancer endothelium, thereby highlighting the cytokine and its cognate receptor as potential targets for the antiangiogenic treatment of this disease.

Doctor, Does This Mean I'm Going to Starve to Death?

Here’s the Case “Shirley” is a 60-year-old woman who presented with abdominal pain and distension 10 years ago. Following a total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy she had been diagnosed with an International Federation of Gynecology and Obstetrics stage IC poorly differentiated endometrioid cancer of the ovary and had subsequently received six cycles of carboplatin, cyclophosphamide, doxorubicin, and ifosfamide. She was well until 3 years ago, when a computed tomography scan showed extensive disease in the omentum and pelvis. A laparotomy revealed inoperable intra-abdominal disease that was histologically consistent with recurrent ovarian cancer. She received six cycles of carboplatin and paclitaxel. A computed tomography scan confirmed a partial response, and Shirley remained well until 2 years ago. At that time, she developed abdominal distension, colic, and flatulence, due to progressive disease. She was treated with single agent carboplatin, but after two cycles, Shirley presented with the symptoms and signs of bowel obstruction. Surgical management was not an option, given the extent of the intra-abdominal disease. Nausea and abdominal discomfort were well controlled medically, and she reported a good quality of life, although she vomited after eating. Following a series of long discussions with Shirley, her relatives, nursing staff, and a number of physicians, a percutaneous venting jejunostomy was fashioned to permit her to eat and drink. This drained 2 L of fluid per day on average. At this point, Shirley and her medical team began to consider whether intravenous nutritional support should be initiated. Ovarian cancer is a common malignancy in the Western world, causing ap

Research priorities for stillbirth: process overview and results from UK Stillbirth Priority Setting Partnership.

†Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK; ‡St Mary’s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; §Library Service, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; ¶Sands (Stillbirth and Neonatal Death Charity), London, UK; **Tommy’s, London, UK; ††NHS Scotland, Edinburgh, UK; ‡‡National Maternity Support Foundation, Jake’s Charity, Hertfordshire, UK; §§British and Irish Paediatric Pathology Association, London, UK; ¶¶Department of Paediatric Pathology, Addenbrooke’s Hospital, Cambridge, UK; ***The Royal College of Midwives, London, UK; †††Holly Martin Stillbirth Research Fund, Powys, UK; ‡‡‡James Lind Alliance, NIHR Evaluation Trials and Studies Coordinating Centre, Southampton, UK *Correspondence. (e-mail: alexander.heazell@manchester.ac.uk)

Early Antenatal Prediction of Gestational Diabetes in Obese Women: Development of Prediction Tools for Targeted Intervention

All obese women are categorised as being of equally high risk of gestational diabetes (GDM) whereas the majority do not develop the disorder. Lifestyle and pharmacological interventions in unselected obese pregnant women have been unsuccessful in preventing GDM. Our aim was to develop a prediction tool for early identification of obese women at high risk of GDM to facilitate targeted interventions in those most likely to benefit. Clinical and anthropometric data and non-fasting blood samples were obtained at 15+0–18+6 weeks’ gestation in 1303 obese pregnant women from UPBEAT, a randomised controlled trial of a behavioural intervention. Twenty one candidate biomarkers associated with insulin resistance, and a targeted nuclear magnetic resonance (NMR) metabolome were measured. Prediction models were constructed using stepwise logistic regression. Twenty six percent of women (n = 337) developed GDM (International Association of Diabetes and Pregnancy Study Groups criteria). A model based on clinical and anthropometric variables (age, previous GDM, family history of type 2 diabetes, systolic blood pressure, sum of skinfold thicknesses, waist:height and neck:thigh ratios) provided an area under the curve of 0.71 (95%CI 0.68–0.74). This increased to 0.77 (95%CI 0.73–0.80) with addition of candidate biomarkers (random glucose, haemoglobin A1c (HbA1c), fructosamine, adiponectin, sex hormone binding globulin, triglycerides), but was not improved by addition of NMR metabolites (0.77; 95%CI 0.74–0.81). Clinically translatable models for GDM prediction including readily measurable variables e.g. mid-arm circumference, age, systolic blood pressure, HbA1c and adiponectin are described. Using a ≥35% risk threshold, all models identified a group of high risk obese women of whom approximately 50% (positive predictive value) later developed GDM, with a negative predictive value of 80%. Tools for early pregnancy identification of obese women at risk of GDM are described which could enable targeted interventions for GDM prevention in women who will benefit the most.

A randomised controlled trial comparing standard or intensive management of reduced fetal movements after 36 weeks gestation-a feasibility study

BackgroundWomen presenting with reduced fetal movements (RFM) in the third trimester are at increased risk of stillbirth or fetal growth restriction. These outcomes after RFM are related to smaller fetal size on ultrasound scan, oligohydramnios and lower human placental lactogen (hPL) in maternal serum. We performed this study to address whether a randomised controlled trial (RCT) of the management of RFM was feasible with regard to: i) maternal recruitment and retention ii) patient acceptability, iii) adherence to protocol. Additionally, we aimed to confirm the prevalence of poor perinatal outcomes defined as: stillbirth, birthweight <10th centile, umbilical arterial pH <7.1 or unexpected admission to the neonatal intensive care unit.MethodsWomen with RFM ≥36 weeks gestation were invited to participate in a RCT comparing standard management (ultrasound scan if indicated, induction of labour (IOL) based on consultant decision) with intensive management (ultrasound scan, maternal serum hPL, IOL if either result was abnormal). Anxiety was assessed by state-trait anxiety index (STAI) before and after investigations for RFM. Rates of protocol compliance and IOL for RFM were calculated. Participant views were assessed by questionnaires.Results137 women were approached, 120 (88%) participated, 60 in each group, 2 women in the standard group did not complete the study. 20% of participants had a poor perinatal outcome. All women in the intensive group had ultrasound assessment of fetal size and liquor volume vs. 97% in the standard group. 50% of the intensive group had IOL for abnormal scan or low hPL after RFM vs. 26% of controls (p < 0.01). STAI reduced for all women after investigations, but this reduction was greater in the standard group (p = 0.02). Participants had positive views about their involvement in the study.ConclusionAn RCT of management of RFM is feasible with a low rate of attrition. Investigations decrease maternal anxiety. Participants in the intensive group were more likely to have IOL for RFM. Further work is required to determine the likely level of intervention in the standard care arm in multiple centres, to develop additional placental biomarkers and to confirm that the composite outcome is valid.Trial registrationISRCTN07944306

The design of a community lifestyle programme to improve the physical and psychological well-being of pregnant women with a BMI of 30 kg/m2 or more.

BackgroundObesity is a global public health issue. Having a BMI of 30 kg/m2 or more (classifying a person as obese) at the start of pregnancy is a significant risk factor for maternal and fetal morbidity. There is a dearth of evidence to inform suitable inteventions to support pregnant women with a BMI of 30 kg/m2 or more. Here we describe a study protocol to test the feasibility of a variety of potential healthy lifestyle interventions for pregnant women with a BMI of 30 kg/m2 or more in a community based programme.Methods/DesignFour hundred women will be approached to attend a 10-week community lifestyle programme. The programme will be provided as a supplement to standard antenatal care. The programme is multi-faceted, aimed at equipping participants with the skills and knowledge needed to adopt healthy behaviours. The social (cognitive) learning theory will be used as a tool to encourage behaviour change, the behaviour change techniques are underpinned by five theoretical components; self-efficacy, outcome expectancies, goal setting, feedback and positive reinforcement.The main outcomes are pregnancy weight gain and caesarean section rate. Other important outcomes include clinical outcomes (e.g., birth weight) and psychological outcomes (e.g., well-being). Secondary outcomes include womens experience of pregnancy and health care services, amount of physical activity, food intake and the suitability of the intervention components.A prospective study using quantitative and qualitative methods will inform the feasibility of implementing the community lifestyle programme with pregnant women with a BMI of 30 kg/m2 or more. Mixed methods of data collection will be used, including diaries, focus groups/interviews, pedometers, validated and specifically designed questionnaires, a programme register, weight gain during pregnancy and perinatal outcome data.DiscussionFindings from this current feasibility study will inform future interventions and NHS services and add to the evidence-base by providing information about the experiences of pregnant women with a BMI of 30 kg/m2 or more undertaking a community lifestyle programme. The study will lead on to a randomised control trial of a suitable intervention to improve the pregnancy outcomes of this target group.Trail RegistrationISRCTN29860479.

Evaluation of the quality of guidelines for the management of reduced fetal movements in UK maternity units

BackgroundThe development of evidence-based guidelines is a key step in ensuring that maternity care is of a universally high standard. To influence patient care national and international guidelines need to be interpreted and implemented locally. In 2011, the Royal College of Obstetricians and Gynaecologists published guidelines for the management of reduced fetal movements (RFM), which can be an important symptom of fetal compromise. Following dissemination it was anticipated that this guidance would be implemented in UK maternity units. This study aimed to assess the quality of local guidelines for the management of RFM in comparison to published national standards.MethodsCross-sectional survey of maternity unit guidelines for RFM. The guidelines were assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II Tool and scored by two independent investigators. Two national guidelines were used as standards to evaluate unit guidelines.ResultsResponses were received from 98 units (42%); 12 units had no guideline. National guidelines scored highly using the AGREE II tool but there was wide variation in the quality of individual maternity unit guidelines, which were frequently of low quality. No guidelines incorporated all the recommendations from the national guideline. Maternity unit guidelines performed well for clarity and presentation but had low scores for stakeholder involvement, rigour of development and applicability.ConclusionsIn contrast to national evidence based guidance the quality of maternity unit guidelines for RFM is variable and frequently of low quality. To increase quality, guidelines need to include up to date evidence and audit standards which could be taken directly from national evidence-based guidance. Barriers to local implementation and resource implications need to be taken into consideration. Training may also improve the implementation of the guideline. Research is needed to inform strategies to realize the benefits of clinical guidance in practice.

Investigations following stillbirth – which tests are most useful and cost effective?

Background The RCOG guideline on the management of stillbirth recommends a variety of investigations to identify potential causes including: post-mortem (PM), placental histopathology and blood tests. There is little data regarding the detection rates of these investigations and this strategy has significant cost implications, we estimate that the complete investigations cost £1283 per case, giving a national annual cost of ∼£5.2M. We aimed to determine which investigations are done after stillbirth and which are most cost-effective. Methods All stillbirths between October 2009 and December 2010 were reviewed (n=44). We determined which investigations were undertaken and whether they provided information which changed or supported the diagnosis of conditions linked to stillbirth. Cost effectiveness was calculated as cost/number of cases diagnosed. Results The uptake of investigations was: PM (36%), placental histology (80%), HbA1c (36%), bile acids (20%), pre-eclampsia screen (34%), thrombophilia screen (66%) and cytogenetics (30%). No patients had a complete set of investigations despite the presence of a guideline. The cost per information obtained was greatest for cytogenetics (£3069) and least for bile acids (£45). Placental histology was more cost effective than PM (£102 vs £1733). Conclusions The presence of a clear guideline does not guarantee complete investigation of cases of stillbirth. Although this data is preliminary, it suggests that some investigations (placental histology and serum biochemistry) may be more cost effective than others, which may be selected for specific circumstances. Large scale studies involving health economics are needed to determine which investigations are most appropriate after stillbirth.